The goals of this paper were to compare baseline rates of MCI and rates of progression to dementia over six years, using different MCI diagnostic systems. 40.2% of individuals were identified as MCI using a CDR score of 0.5 and 28.2% using NP criteria (amnestic and nonamnestic combined). There was agreement between the two diagnostic methods in over 63% of cases, 47.4% were classified as Normal by both criteria (NP Normal/CDR Normal) and 15.7% were classified as MCI by both criteria (NP MCI/CDR MCI). There were no significant differences between the four subgroups (congruent and incongruent) in the number of medications reported and the number of deaths but there were a higher number of drop-outs in the group meeting both sets of MCI criteria. The percentage of ApoE4 carriers also did not differ between subgroups and is similar to that reported in other community studies (CHS, 24.1%) [33
] although lower than observed in some clinical samples [34
]. Not surprisingly, individuals diagnosed as MCI by both methods were older, sicker, and more functionally and cognitively impaired.
Our overall rate of amnestic MCI (16.6%) as determined by neuropsychological algorithm is comparable with other studies, although comparison is difficult because different criteria were used. [20
] However, our rate of MCI using CDR criteria (40.2%) is higher than other studies, for example, Meguro and colleagues [37
] who reported an overall frequency of CDR 0.5 of 30.2%. The main purpose of this study, however, was not to compare rates of MCI in the GEM study to other population studies but rather to compare the rates of MCI using the two approaches within the same cohort. We found that the two diagnostic methods were largely concordant for the identification of Normal individuals but there was lower agreement for the identification of MCI and, furthermore, there were a surprisingly high number of individuals who either had normal test performance but CDR scores of 0.5 or impaired test performance and CDR scores were 0. Similar rates of MCI were reported in patients attending a memory clinic [38
] using a Global Deterioration Scale [39
] score of 2 or 3 as the measure of subjective cognitive complaints and a NP definition of a-MCI.
Our results suggest that individuals with normal cognition but CDR-measured deficits are more likely to have lower education; endorse a higher number of health, and report symptoms of depression (but not meet formal criteria for a diagnosis of depression) than those without CDR-measured deficits. Depression is common in preclinical AD and can be an early sign of a neurodegenerative disorder [38
]. Our results also suggest that the CDR is sensitive to very subtle differences in cognition. Thus, among individuals who were classified as Normal by the NP algorithm, the CDR classified, on average, those with higher test scores as CDR Normal and those with poorer scores as CDR MCI and, similarly, among individuals classified as MCI by the neuropsychological algorithm, the CDR classified those with higher test scores as CDR Normal those with lower scores as CDR MCI.
In this study the majority of individuals with MCI did not progress to dementia over the follow-up period. This finding is consistent with other studies of community-dwelling elderly [41
] and also clinic populations [38
]. The rates of dementia identified by different MCI diagnostic criteria are also consistent with other studies which show that a slightly higher percentage of individuals convert to dementia using cognitive test scores as a predictor than using functional criteria [38
]. Reported conversion rates based on a CDR 0.5 definition of MCI vary across studies [6
] and may be related to the broad range of functional disability that falls within the CDR 0.5 category. For example, a CDR 0.5 sum of box score of 2.0 or higher has been shown to accurately predict 50% or higher conversion rate to AD over 3 years compared to a 10% conversion rate for individuals with a CDR 0.5 sum of box score of 1.0 [43
]. The specific clinical subtype of CDR 0.5, as determined by clinical impression, has also been shown to predict conversion rates to dementia with 60.5% of individuals classified as “CDR 0.5 Dementia of the Alzheimer's Type” (DAT) and 35.7% of individuals classified as “CDR 0.5 Incipient DAT” progressing to dementia over 5 years [6
]. Our findings show significantly higher rates of conversion to dementia (41.5%) when individuals meet both MCI criteria compared to individuals who meet both Normal criteria (7.5%). Significant differences were also observed in the two incongruent groups. Although the rates are similar, a higher percentage of those classified as NP MCI/CDR Normal progressed to dementia (22.8%) than those classified as CDR MCI/NP Normal (17.2%), suggesting that poor performance on neuropsychological tests is a slightly better indicator of future progression to dementia than functional impairment.
Several factors may contribute to our findings. First, these data were gathered as part of a clinical trial and it is possible that G. biloba
had an effect on the progression to dementia in one group over another. However, we have previously reported that G. biloba
was not effective in lowering either the overall incidence rate of dementia or AD incidence in normal elderly or persons with MCI; nor was there any effect of G. biloba
on mortality, stroke or myocardial infarction [17
] and as a randomized trial it is unlikely there was a disproportionate effect of G. biloba
Second, different findings may occur across studies if the CDR is administered differently. GEM study interviewers completed standardized training procedures and were certified by one of the co-authors (LOD) who has had more than ten year's experience as a CDR trainer. We also considered the possibility that community informants are not as reliable as informants in clinical settings but the majority of GEM informants lived with the participant and of those informants who did not, most reported visiting at least once a week. Furthermore, we found little difference in CDR classification based on informant characteristics suggesting that information obtained from GEM informants was reliable. There is also the possibility of circularity in our diagnosis of MCI and dementia, both of which used performance on the neuropsychological battery. However, the dementia diagnosis was not limited to the neuropsychological battery but involved a comprehensive review of clinical assessments across multiple years and included performance on screening tests (3MSE and the ADAS-Cog) not used in the MCI or dementia algorithm. Finally, although the participants in this study were drawn from the community they are a unique hybrid of a representative community sample but with a clinical trial selection bias. This sample may not be typical of the referral population seen in most clinical trials but also is not an epidemiological community cohort and this may also contribute to our findings. However, having said this, the critical finding in this study is not the overall rates of MCI compared to other studies, but the comparison of the two classification methods within the same cohort. Nevertheless, the sample may include large numbers of so-called, “worried well” who have more subjective complaints of memory loss, depression and poor health and this may contribute to higher rates of CDR 0.5.
Finally, proponents of the CDR have suggested that, when followed longitudinally, the majority of individuals with CDR 0.5 progress to AD and, based on this finding, they suggest that a CDR of 0.5 more correctly represents early mild AD rather than MCI.[6
] The implications of this suggestion are potentially enormous, especially considering that more than 40% of individuals in this study received a CDR of 0.5 at baseline. Our findings confirm that the CDR picks up subtle cognitive loss but also suggests that the CDR is sensitive to subtle psychiatric and clinical factors and that these also influence the likelihood that an individual will be classified as MCI by the CDR. In one of the few studies addressing this issue, the Helsinki Aging Study[44
] administered the CDR as part of a dementia work-up for 900 individuals between the ages of 75 and 80 living in the city of Helsinki. The CDR was completed by community physicians who, contrary to standard guidelines, were instructed to record CDR deficits related to any reason, not only cognition. Thirty-two individuals scored 1.0 on the CDR, indicating the presence of dementia, but in a follow-up neurological evaluation were assessed by a neurologist as not suffering from dementia. As in our study, discordant diagnoses were associated with the presence of psychiatric symptoms (37%), especially depression (28%), and medical disorders (47%).
In conclusion, using different MCI criteria, we identified different rates of MCI at baseline and different rates of progression to dementia over time. CDR ratings of MCI were influenced by a number of demographic, cognitive and clinical factors some of which may be more relevant to the identification of MCI within community cohorts than in memory clinics where patients present with existing memory complaints. Slightly more individuals meeting NP MCI criteria progressed to dementia over the follow-up than individuals identified as MCI by the CDR. These results suggest that identifying all individuals with CDR scores of 0.5 as AD is not advisable.